Mycobacterium abscessus subsp. massiliense: Biofilm Formation, Host Immune Response, and Therapeutic Strategies

Abstract

Infection by Mycobacterium abscessus subsp. massiliense poses a growing public health threat, especially to immunocompromised individuals. The pathogenicity of this mycobacterium is directly linked to its ability to form biofilms, complex structures that confer resistance to antibiotics and the host immune response. The extracellular matrix of the biofilm acts as a physical barrier, hindering the penetration of drugs and the action of the immune system, while also inducing a slow-growth state that reduces susceptibility to antibiotics. Current therapies, which involve prolonged use of multiple antibiotics, are often ineffective and cause significant side effects. Therefore, it is essential to explore new strategies targeting bacterial resistance and biofilm destruction. This narrative review explores the biofilm-forming capacity of Mycobacterium abscessus subsp. massiliense and the potential of novel therapeutic strategies. Promising approaches include inhibiting biofilm formation, developing drugs with improved penetration of the extracellular matrix, combination therapies with agents that destabilize the biofilm structure, and modulating the host immune response. Investing in research and development of new therapeutic strategies is essential to combat this resistant bacterium and improve patient outcomes.

Keywords: Mycobacterium abscessus subsp. massiliense; biofilm; immune response.

Figure 1

Schematic representation of the mycobacterial cell envelope. GPLs are specific to the smooth [S] variant cell wall and are transported across the inner membrane by MmpL4a and MmpL4b proteins. Other MmpL proteins may function as drug efflux pumps, contributing to intrinsic antibiotic resistance. The type VII secretion system [ESX-4], responsible for translocating EsxT and EsxU effectors, plays a key role in intracellular survival and bacterial pathogenesis. Legend: LAM [lipoarabinomannan], LM [lipomannan], PIM [phosphatidyl-inositol mannoside], PL [phospholipid], TDM [trehalose dimycolate], TPP [trehalose polyphleate], and TMM [trehalose monomycolate]. Figure created with BioRender.com.

Figure 2

Mechanisms of immune evasion by M. abscessus. The smooth colony morphotype, expressing GPLs, “masks” immune recognition molecules such as PIMs and prevents the bacterial interaction of lipids like trehalose polyphleates. This action facilitates pulmonary colonization. The loss of GPLs leads to recognition by TLR2, resulting in the release of pro-inflammatory cytokines. The rough morphotype, more virulent, grows in serpentine cords, inducing macrophage apoptosis to disseminate the infection. This figure was created with BioRender.com.

Figure 3

Schematic representation of M. abscessus biofilm formation and antibiotic resistance. Biofilm formation begins with the reversible attachment of planktonic cells [dark green] to a surface [blue]. The bacteria then form a monolayer and irreversibly adhere, producing an extracellular matrix. A microcolony forms, with multilayered growth appearing. In later stages, the biofilm matures. Finally, some cells begin to detach, and the biofilm disperses. The inherent resistance of M. abscessus subsp. massiliense is attributed to factors such as an impermeable and serous cell wall that acts as a physical [size exclusion] and chemical [hydrophobic] barrier, drug export systems, enzymes that modify or target drugs, and genetic polymorphisms in target genes. This figure was created with BioRender.com.

Figure 4

Number of annual publications from 2000 to 2025 on new therapeutic strategies for M. abscessus infections.